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Eva Gallardo, MDMedical Manager, Biocompatibles UK

Drug Eluting Bead: Clinical Updates and Histological Data

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Doxorubicin Bead Irinotecan Bead

Primary Liver Cancer Colorectal MetastasesVery Early/Early Stage Prior to resection Bridge to transplant RFA + PRECISION TACE

Intermediate Stage Precision I Precision II Precision V

Advanced Stage Sorafenib + PRECISION TACE

Secondary Liver Cancer Other Primary Cancers

Renal Breast Melanoma Gastric Neuroendocrine Cholangiocarcinoma Sarcoma

Early CT Lines

Late Stage

DC Bead: Clinical Programme

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Investigators: Camillo Aliberti, MD Giammaria Fiorentini, MD

Department of Diagnostic and Interventional Radiology,Delta Hospital AUSL Ferrara, Ferrara Italy

Department of Oncology, General Hospital San Giuseppe, Empoli, Florence, Italy

PRECISION TACE in treatment of Colorectal Metastases

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• 62 patients (M/F = 42/20), median aged 64.6 (range 42-85)

• Not operable and pretreated at least two lines of chemo (range 2-6)

• Maximum dose 4 ml (2ml of 100-300mm and 2ml of 300-500mm) with 200mg of Irinotecan

• 2-3 TACE 4 weeks

Irinotecan Bead in Advanced Colorectal Cancer: Patient

Selection

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Postembolization-syndrome

RUQP (G2-G3) 100%

Fever (G2) 90%

Nausea and Vomiting (G2-G3)

100%

Increased Transaminases (G2-G3)

80% 0

5

10

15

20

25

30

35

40

Procedures

Pain Vomiting Fever Asthenia

Irinotecan Bead in Advanced Colorectal Cancer: Toxicity

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• The median follow-up was 15.4 months

• 1 month CT scan showed reduction of metastatic CE 85%, range 75-100% in all patients

• RECIST at 3 months: 78%

• 55/62 pts (90%) declared a general improvement of QoL lasting 6.5 months, range 3-12 

Irinotecan Bead in Advanced Colorectal Cancer: Response to

Treatment

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• Median survival not reached at 22 months

• Median Free Time from symptoms 5.3 (5-20 months)

• Median Time to further chemoteraphy 6.3 (5-22 months )

0

10

20

30

40

50

60

70

80

90

100

0 2 4 6 8 10 12 14 16 18 20 22time months

surv

ival

(%

)

Irinotecan Bead in Advanced Colorectal Cancer: Survival

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18 months after TACE

Irinotecan Bead in Advanced Colorectal Cancer: Cases

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02.2005 09.2005

6 months after TACE

Irinotecan Bead in Advanced Colorectal Cancer: Cases

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Principal Investigator: Thierry De Baere, MDChief of Interventional Radiology Department

Institut de Cancérologie Gustave Roussy - Villejuif - France

Neuroendocrine Metastasis

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Doxorubicin Bead in NET:Materials and Methods

• 20 patients with liver metastases from low-grade GEP tumour

• Progressive liver disease on two subsequent imaging studies according to RECIST criteria

• Disease predominant to the liver

• Up to 4ml DC Bead 500-700mm loaded with up to 100mg doxorubicin

• Concomitant treatment with long-acting ST analog

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Doxorubicin Bead in NET:Results

• 34 sessions (6 unilobar, 14 bilobar)

• RECIST 3M: – 16/20 (80%) partial response– 3/20 (10%) stable disease– 1/20 (15%) progressive disease

• After a median follow-up of 15 months (6-24), disease remained controlled without tumour progression in 45%

• 1 patient become resectable

Progression

161520

0%10%

20%30%

40%50%60%

70%80%

90%100%

0 6 12 18 24Months since treatment

Pro

gre

ssio

n r

ate

Patients at risk

At 12 months : 47% (95%CI = 23% - 72%)

Median Time to Progression: 15 months

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• Post-embolisation syndrome:– < 7 days in 67% sessions– > 7 days in 22% sessions– No symptoms in 11% sessions

• Hypodense subsegmental peripheral areas (TACE-induced necrotic liver tissue?) in 5 patients at 1 month CTscan

• 1 death: resected patient due to postoperative septic complications

Doxorubicin Bead in NET:Toxicity

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Doxorubicin Bead in NET:Cases

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Doxorubicin Bead in NET:Cases

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Principal Investigator: Riccardo Lencioni, MDAssociate Professor of Diagnostic and Interventional

RadiologyDepartment of Oncology, Transplants, and Advanced

Technologies in Medicine – Pisa University, Italy

Combined PRECISION TACE/RFA: Results and Outcome

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Vessel

Sub-lethal heating(45-50 °C)

50 °C

RFA: Inherent Limitations

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DEB-Enhanced RFA of HCC: A Pilot StudyDesign / Enrollment Criteria

20 pts (mean age, 70 ± 6 ) with residual viable tumour at CT / MRI 1-2 hrs after RFA

- Tumour diameter 3.3-7.0 cm (mean, 5.0 cm ± 1.4)- Child-Pugh class A, ECOG 0- PT ratio > 50%, platelets > 50,000/mm3

Excl: - Eligibility for liver resection or transplantation- Vascular invasion / extrahepatic disease

- Any previous treatment for HCC

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DEB-Enhanced RFA of HCC: A Pilot StudyMaterials and Methods

Follow-up period 6-20 months (mean, 12 months ± 5)

DC Bead (Biocompatibles) injection < 24 hrs of RFA

- 50 mg doxorubicin in 2 ml of 100-300 μm beads - Additional loads (100-300 / 300-500 µm) if needed

Tumour response: RECIST criteria - EASL amendment

- CR: absence of enhancement at 1-month CT / MRI- Confirmed CR: CR lasting no less than 6 months- OR: confirmed CR target lesion, no new lesions

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61% +

Abl

atio

n V

olum

e (m

m3)

0,000

20,000

40,000

60,000

80,000

100,000

120,000

140,000

160,000

180,000

Standard RFA DEB-Enhanced RFA

DEB-Enhanced RFA of HCC: A Pilot StudyResults – Change in Ablation Volume

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DEB-Enhanced RFA of HCC: A Pilot StudyResults – Clinical Case # 2

Pre-treatment CT

6 cm

Post-RFA Post-TACE

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Target lesions

Table. Overall Response at the End of Follow-Up

New lesions

CR

PR

CR / PR

PD

Note: Numbers are numbers of patients. Overall number of patients: 20.

No

No

Yes

Yes / No

Overall response

CR

PR

PD

No. (%)

10 (50%)

5 (25%)

3 (15%)

2 (10%)

DEB-Enhanced RFA of HCC: A Pilot StudyResults – Overall Response

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0 6 12 18 240

20

40

60

80

100

DEB-enhanced RFA (n = 20)

months

30

100%

DEB-Enhanced RFA of HCC: A Pilot StudyResults – Overall Survival

92%

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Doxorubicin Bead prior to liver transplant

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TACE Prior to Transplant

• Major issue = Dropout rate (30-40%)Major issue = Dropout rate (30-40%)

• Role of TACE:Role of TACE:• Patients within Milan criteria (maintain in waiting list)Patients within Milan criteria (maintain in waiting list)• Patients outside Milan criteria (for downstaging to fullfil Patients outside Milan criteria (for downstaging to fullfil

Milan criteria)Milan criteria)

• Induce high hystological tumour response rateInduce high hystological tumour response rate

• Decrease recurrence rates?Decrease recurrence rates?

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Dr Citron –Atlanta, US

• Retrospective study• 9 listed patients (>Child A-B, single nodules, mean

tumour size 2cm (0.3-5.1)• 1-3 treatments prior to transplant• 100-300 and/or 300-500mm DC Bead with up

150mg doxorubicin• Liver transplant (1-281 days post-treatment)

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Results

• CTscan:– Complete necrosis 88% patients

• Histology:– Complete necrosis 77% patients– 2 non-complete necrosis:

• Patient transplanted 8 hours after TACE with no necrosis• Patient with residual 0.5cm viable tumour within 7.5cm

necrotic tumour

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Dr Nicolini - Italy• Retrospective study Doxorubicin Bead vs TAE• 16 patients (15 waiting list/ 1 outside Milan)

DC Bead TAE

HCV

HDV + HBV

Others

3

3

2

4

0

4

Child-Pugh A

Child-Pugh B

5

3

6

2

Mean tumour size (cm) 3.0 3.4

Single

2 nodules

7

1

5

3

•1-4 treatments until complete RX response•DC Bead arm: 100-300mm DC Bead with 50mg epirubicin•TAE:100-300mm Embosphere

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Tumour ResponseDC Bead TAE

CTscan Response*

Complete Necrosis

Partial Necrosis (>70%)

88

12

45

55

Histological Response*

Complete Necrosis

Necrosis >70%

Necrosis <50%

78

22

0

P=0.04

27

54

19

* % Tumour response by tumours

• 62.5% DC Bead achieved complete RX response after one treatment vs 12.5% in TAE

• 15 patients alive with no recurrence

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Prof Goffette - Belgium• 16 patients:

– 9 within the Milan criteria for LT– 7 outside the Milan criteria for LT

• Diameter > 5 cm 4• More than 3 tumours 3

• Mean tumour size 5.4 cm (2.3-7.8) , 2 portal vein thrombosis• Standardized DC Beads doses and sizes:

– 4ml (2 vials) of 300-500 µm particles loaded with 25mg/ml doxorubicin:100 mg Doxo/session

• Additional unloaded particles (300-500,500-700µ) if persitent flow• Sequential treatment every 3 months (Max 4)• Alternate treatment if bi-lobar lesions

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Procedural Results• Mean number of sessions 2.7

4pts:1, 6pts:2, 7pts:3, 1pt:4

• Serious adverse event

Cholecystitis 1

• 30-day mortality 0

• Post-embol syndrome 15

• Transient impaired liver function 12

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• Transplanted patients 10

• Delay: 6.5 months (2-15)

• Biliary complications: 3• Follow-up: 7.5 months

– 1 recurrence at 5 m (40% necrosis)

• Patients on waiting list 4

• Deaths 2

• Pneumonia

• Terminal liver failure

• Significant downstaging in 6/7 patients

Clinical Results

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• Complete 4(25%)

• Partial 11(69%)– Residual peripheral enhancement 9– Persistent enhanced nodules 4

• Stable Disease 1

• Progressive Disease 0

• Objective Response 15(94%)

Results Imaging (EASL)

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Histological Response

PATHOLOGIC ASSESSMENT

All

patients

(n=12)

Vascular permeation

Portal thrombosis

Recurrence

After OLT

(n=10)

RESPONSE

Complete

tumor necrosis5 (42%) 0 0/5 (0%)

Partial

tumor necrosis ≥75%

and <99%

6 (50%) 2 0/4 (0%)

NO RESPONSEIncomplete

tumor necrosis < 50%

1 (8%) 1 1/1 (100%)

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Surgical Complications

• Complicated arterial anastomosis 7 – Co/proper Hep. Art. occlusion

4– Pedicular inflammation

3– Early arterial occlusion…redo-OLT in 1

• Difficult biliary anastomosis 3

• Severe chronic cholecystitis 4

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46 yr old male: Bilobar HCC ( >7cm seg IV)Downstaging before LT

First TACE session left lobeFirst TACE session left lobe

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Repeated controls CT after first sessionRepeated controls CT after first session

Second TACE (right lobe) and control CT……waiting listSecond TACE (right lobe) and control CT……waiting list

46 yr old male: Bilobar HCC ( >7cm seg IV)

Downstaging before LT